A new study in the Journal of Hepatology adds NAFLD to the list of diseases associated with a Western diet that includes relatively high consumption of red and processed meat

World meat consumption has increased during the last decades, and evidence is mounting that high consumption of red and mainly processed meat is unhealthy to humans and is related to chronic diseases such as cancer, type 2 diabetes, and cardiovascular disease. A new study published in the Journal of Hepatology adds non-alcoholic fatty liver disease (NAFLD) to the list.

“NAFLD is considered as the hepatic component of the metabolic syndrome, with insulin resistance and inflammation as key factors in its pathophysiology,” explained lead investigator Prof. Shira Zelber-Sagi, RD, PhD, from the School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Israel. “Unhealthy Western lifestyle plays a major role in the development and progression of NAFLD, namely, lack of physical activity and high consumption of fructose and saturated fat. Our study looked at other common foods in the Western diet, namely red and processed meats, to determine whether they increase the risk for NAFLD.”

In order to test the association of type of meat and cooking method with NAFLD and insulin resistance, investigators undertook a cross-sectional study among individuals 40-70 years old who underwent screening colonoscopy at the Department of Gastroenterology and Hepatology in the Tel Aviv Medical Center, and who agreed to participate in a metabolic and hepatic screening study between 2013 and 2015.

NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment (HOMA). Meat type and cooking method were measured by food frequency and detailed meat consumption questionnaires. Unhealthy cooking methods were characterized as frying or grilling to a level of well done or very well done. These methods produce heterocyclic amines (HCAs), which are pro-inflammatory compounds, and their intake was also calculated.

After excluding some of the participants due to factors such as viral liver disease and alcohol abuse, close to 800 subjects were included in the main analysis, of whom a sub-sample of 357 subjects completed the meat questionnaire. NAFLD was diagnosed in 38.7 percent of participants and insulin resistance in 30.5 percent. The proportion of red and white meat intake was about one third and two thirds, respectively, which is similar to the typical diet of the Israeli population. High meat eaters were slightly younger, mainly male, had a higher body mass index (BMI), caloric intake, and a worse metabolic profile.

The results showed that high consumption of red and processed meat is independently associated with NAFLD and insulin resistance regardless of saturated fat and cholesterol intake and other risk factors such as BMI. In addition, individuals who consumed large quantities of meat cooked using unhealthy methods and those already diagnosed with NAFLD who consumed high HCAs had a higher chance of having insulin resistance.

Low carb diets are frequently recommended to prevent metabolic diseases. These low carb diets can be very rich in animal protein, especially meat. While meat contributes valuable nutrients that are beneficial to health, including protein, iron, zinc, and vitamin B12, the current study indicates that meat should be eaten in moderation and the type of meat and its preparation method should be wisely chosen.

Although the association between high red and processed meat consumption and NAFLD remains to be confirmed by prospective studies, Prof. Zelber-Sagi, recommends limiting red and processed meat consumption in preference for healthier “white meat,” such as chicken or turkey, including fish in the diet, and steaming or boiling food instead of grilling or frying meat at a high temperature until it is very well done.

“NAFLD is primarily a lifestyle-oriented disease. With sound medical and nutritional guidance from their clinicians, patients are better informed and equipped to implement the lifestyle changes needed to help reverse this disease,” remarked Prof. Zelber-Sagi.

More and more young girls seek help for mental problems. “Generally, girls take things more seriously than boys. This applies to school, friends and family,” says researcher Anders Bakken.

“We see that the share of young girls between the age of fifteen and twenty who seek help for mental disorders is increasing,” says Anne Reneflot. She is Department Director at Norwegian Institute of Public Health and one of the authors behind a new report on mental health in Norway.

Today, seven per cent of all girls between the age of fifteen and seventeen, and nine per cent between eighteen and twenty are diagnosed with mental disorders. Over the past years, the amount of girls within the age group who are prescribed anti-depressants have doubled from approximately one to two per cent.

Gender differences

Forty per cent more seek help than five years ago.

“The most common mental problems among girls in this age group are anxiety, depression, eating disorders and adjustment difficulties,” she says.

The report does not show the same pattern among boys in the same age group. Instead, boys with mental disorders are more often diagnosed before they reach puberty, and have a higher risk of being diagnosed with ADHD, autism and Tourette’s syndrome.

“In addition to an increase in young girls who seek help, we also see a rise in the use of anti-depressants.”

“Do you know anything about why more young girls seek psychiatric help?”

“No. All we know is that more young girls seek help, but we are not certain whether it is because the actual scope of mental illnesses has increased,” says Reneflot.

“It may also have to do with an increased openness in society and awareness of the possibilities for help. And the fact that there are more mental healthcare services. But this is only speculations.”

Adjustment difficulties are among the mental problems for which more and more young girls seek help. These are mental problems triggered by distressing life incidents, according to Reneflot.

“Examples of such distressing life incidents may be changes or problems connected to family or school,” she says.

Not chronic illnesses

“It is important to distinguish between diagnoses and general mental conditions when we talk about youth and mental health. Many people mix these two, particularly in the media,” says sociologist and researcher Anders Bakken at OsloMet – Oslo Metropolitan University.

Bakken has done research on youth since the mid-1990s, and is director of Ungdata (‘Youthdata’). According to him, the increased share of young girls seeking help from the mental healthcare services both receive and deserve much attention. Nevertheless, he is careful to distinguish between diagnosed mental disorders, which according to him apply to a relatively small share of young people, and general mental conditions that apply to many more in certain periods.

“By general conditions, we’re talking about sleeping disorders, anxiety and stress, problems that affect every one in four girls in their mid-teens.”

Bakken emphasises that this may affect schoolwork and quality of life, but for most people they are not lifelong illnesses.

“But we see more and more girls report such conditions. Thus, although we are not talking about chronic diseases, we should definitely take them seriously. And we do. Both municipalities and schools are constantly initiating new measures to prevent mental problems among youth.”

Openness does not explain everything

Bakken is sceptical towards explaining the increase in girls who seek help with more openness about mental problems.

“Some point towards over reporting. Others claim that we pamper the young and make them more vulnerable and less capable of handling hardship. But if this was the only explanation, we would probably have seen an increase of mental problems among all youth,” he says.

“More and more girls report that they have mental problems. At the same time, we see a higher increase among ethnic Norwegian girls than among girls with minority background, and we see a higher increase among those who are unhappy in school than among those who enjoy school.”

“Why do girls struggle more than boys?”

“Some of it may have to do with biological differences between girls and boys. The fact that more girls report mental problems may, for instance, be because girls mature earlier than boys do. Moreover, boys and girls are often socialised in different directions,” says Bakken.

“We also need to remember that there are huge differences between girls; not all girls struggle. And at the same time, there are also many boys who struggle mentally.”

“Whereas relatively few report mental health problems when in primary school, something happens during the first years in lower secondary. In tenth grade, the figures are much higher,” Bakken explains.

Boys are more playful

He believes boys’ and girls’ different attitude to life may be part of the explanation to why girls struggle.

“Girls generally take things more seriously than boys. This applies to school, friends and family. For instance, we see that girls work harder in school and do more homework than boys do. And they feel more pressure from their surroundings.”

If you take life more seriously, chances are bigger that you have more worries, according to Bakken.

“Boys are more playful and have a tendency to dismiss the problems they are facing. If problems arise, many of them just start doing something else instead, or look the other way.”According to Bakken, the questionnaires used by Ungdata has been criticised for not being able to underpin boys’ problems.

“It may have to do with how the questions are formulated. If a question begins with ‘Do you feel that …’, it may perhaps not appeal to boys to the same extent,” says Bakken.“But at the same time, we also pose a lot of gender neutral questions where girls still score higher than boys, such as ‘Have you had sleep disorders?’”

He emphasises that boys face other challenges; for instance, they are more often involved with crime and violence than girls are.

School matters the most

“What factors affect young girls’ mental health?”

“School stands out as an important factor. There is much pressure on school results among Norwegian youth today. Many are very busy at school, with tests and exams. Most Norwegian youth think it is important to get an education,” says Bakken.

“In one survey, we interviewed tenth graders, and two thirds of the girls and one third of the boys reported that they experience much school related pressure.”

Bakken draws lines back to the Knowledge Promotion Reform (Kunnskapsløftet) in 2006, and argues that since then there has been an increased attention towards school performance. “There has been much talk about how Norwegian pupils perform in each region compared to other countries.”

Nevertheless, Bakken does not want to turn school into the big, bad wolf.

“The level of satisfaction is high in Norwegian schools. But it is important to look at how the schools are run and how it affects the pupils. For some it may have negative effects.”

“Many think that girls experience more body-image pressure than boys. In any case, more girls struggle with eating disorders. May this be a reason why more girls struggle?”

“I haven’t done any research on this. But since 2017, Ungdata has included new questions that address body-image issues among other things. So we will know more about this soon.”

Bakken emphasises that many worry that youth, and particularly young girls, experience increased body-image pressure through social media. But social media also have positive effects on the girls.

“Many girls said that they consider social media a free space and a way in which to keep in touch with friends. Nevertheless, having to be always available and having to respond to messages all the time was also a stress factor.”

Increased focus on the body

According to the report from Norwegian Institute of Public Health, the most common problems among young girls who seek help from the mental healthcare services are anxiety, depression, eating disorders and adjustment difficulties. According to Kari Løvendahl Mogstad, it is difficult to determine to what extent eating disorders are caused by increased body-image pressure. She is general practitioner, sports physician, and university lecturer at Norwegian University of Science and Technology (NTNU), and author of the book Kroppsklemma (‘The body squeeze’).

“The causes behind eating disorders are very complex and complicated, and there is a lot we don’t know about the connections here,” she says.

“What characterises people with eating disorders is low self-esteem, and they seek some kind of control over their own thoughts and feelings by controlling their food intake.”

According to Mogstad, the low self-esteem may be caused by difficult emotions and experiences in life that they have not learned to handle in other ways.

“But there is no doubt that the huge and increasing focus on the body and the pressure from society on young people in particular cause more people to have a difficult relation to food. Some of these also develop eating disorders.”

Mogstad refers to both Norwegian and international studies showing that the focus on the body has increased in society in general, and that this affects how we feel.

Affected by social media

“Over the past ten years, since social media entered the scene, we have become far more exposed to pictures of ‘perfect’ bodies and people than we used to,” she says.

“Growing up today, being bombarded with pictures and constantly reminded that you are not good enough, of course does something with most people’s self-esteem and body-image.”

Studies show that the majority of those who develop eating disorders are girls, but Mogstad believes that there is a lot of under-reporting when it comes to boys and eating disorders.

“Boys and girls have different ways of communicating, and it is perhaps not as accepted for a boy to say publicly that he is struggling with eating disorders,” she says.

“Moreover, girls spend much more time on social media and follow various bloggers, celebrities and others who post pictures of slim and perfect bodies, and they are therefore exposed to more influence from these.”

Facts about the report

In January 2018, Norwegian Institute of Public Health published the report ‘Psykisk helse i Norge’ (‘Mental health in Norway’), a revised version of the report ‘Psykiske lidelser i Norge: Et folkehelseperspektiv’ (‘Mental disorders in Norway: A Public Health Perspective’) from 2009.

The purpose has been to provide an updated overview of the occurrence of mental conditions and substance abuse disorders, and contact with the health services relevant for these disorders.

The idea that it might be possible to be overweight or obese but not at increased risk of heart disease, otherwise known as the “obesity paradox”, has been challenged by a study of nearly 300,000 people published in in the European Heart Journal.

This latest research shows that the risk of heart and blood vessel problems, such as heart attacks, strokes and high blood pressure, increases as body mass index (BMI) increases beyond a BMI of 22-23 kg/m2. Furthermore, the risk also increases steadily the more fat a person carries around their waist.

The study was conducted in 296,535 adults of white European descent who are taking part in the UK Biobank study, and who were healthy at the time they enrolled with the study. UK Biobank recruited from 2006 to 2010, and follow-up data on participants were available up to 2015 for this latest analysis.

Researchers at the University of Glasgow (UK) led by Dr Stamatina Iliodromiti, a clinical lecturer in obstetrics and gynaecology and MRC Fellow, found that people with a BMI between 22-23 kg/m2 had the lowest risk of cardiovascular disease (CVD). As BMI increased above 22 kg/m2, the risk of CVD increased by 13% for every 5.2 kg/m2 increase in women and 4.3 kg/m2 in men.

Compared to women and men with waist circumferences of 74 and 83 cm respectively, the CVD risk increased by 16% in women and 10% in men for every 12.6 cm and 11.4 cm increase in waist circumference for women and men respectively. Similar increases in CVD risk were seen when the researchers looked at waist-to-hip and waist-to-height ratios and percentage body fat mass – all of which are considered reliable ways to accurately gauge the amount of fat a person carries, also known as adiposity.

Although it is already known that being overweight or obese increases a person’s risk of CVD, as well as other diseases such as cancer, there have also been studies that have suggested that, particularly in the elderly, being overweight or even obese might not have any effect on deaths from CVD or other causes, and may even be protective, especially if people maintain a reasonable level of fitness. This is known as the “obesity paradox”.

However, the authors of the EHJ study say their results refute these previous, conflicting findings. “Any public misconception of a potential ‘protective’ effect of fat on heart and stroke risks should be challenged,” said Dr Iliodromiti.

She continued: “This is the largest study that provides evidence against the obesity paradox in healthy people. It is possible that the story may be different for those with pre-existing disease because there is evidence that in cancer patients, for instance, being slightly overweight is associated with lower risk, especially as cancer and its treatments can lead to unhealthy weight loss.

“By maintaining a healthy BMI of around 22-23 kg/m2, healthy people can minimise their risk of developing or dying from heart disease. In terms of other adiposity measures, the less fat, especially around their abdomen, they have, the lower the risk of future heart disease.”

However, the researchers recognise that it can be difficult for some people to maintain a BMI of 22-23 kg/m2, particularly as they get older. Co-author, Naveed Sattar, Professor of Metabolic Medicine at the University of Glasgow, said: “We know many cannot get to such low BMIs so the message is, whatever your BMI, especially when in the overweight or obese range, losing a few kilograms or more if possible, will only improve your health. There are no downsides to losing weight intentionally and the health professions needs to get better at helping people lose weight.”

The researchers say their findings may have implications for guidelines on preventing and managing cardiovascular disease.

“Even within the normal BMI category of between 18.5-25 kg/m2, the risk of CVD increases beyond a BMI of 22-23 kg/m2. The other adiposity measures show that the leaner the person the lower the risk of CVD, and this must be a public message, that healthy individuals should maintain a lean physique to minimise their risk of CVD,” concluded Dr Iliodromiti.

The researchers suggest that the previous confusion over the “obesity paradox” may be due to many factors that can confound results of studies. For instance, smoking changes the distribution of fat in the body, smokers may have lower weight as smoking depresses appetites and so BMI tends to be lower. Another reason could be that some people have existing but undiagnosed disease, which can often lower their weight but also makes them more likely to die prematurely.

Long-term proton pump inhibitor (PPI) use does not increase the risk of hip fracture among persons with Alzheimer’s disease, according to a new study from the University of Eastern Finland. The risk of hip fracture was slightly increased for PPI use of less than one year, but not for long-term or cumulative use during a follow-up period of 10 years. In addition, there were no significant differences between PPI drug substances and the associated risk of hip fracture. The findings were published in Alimentary Pharmacology & Therapeutics.

Some previous studies have suggested that long-term PPI use may increase the risk of hip fracture. According to this new study, however, the risk of hip fracture is not increased even in long-term use. Proton pump inhibitors are effective drugs for dyspepsia, gastroesophageal reflux disease and peptic ulcer and they are commonly and increasingly used among older population.. Due to their gastro-protective properties, they are also co-prescribed with nonsteroidal anti-inflammatory drugs and corticosteroids.

The study is based on the register-based MEDALZ-cohort comprising data on all community-dwelling persons diagnosed with Alzheimer’s disease in Finland in 2005–2011. The study population included 4,818 persons with Alzheimer’s disease and an incident hip fracture, and 19,235 persons without hip fracture. The mean age of the study population was 84 years. For each person with Alzheimer’s disease who experienced their first hip fracture, up to four controls without hip fracture were matched by age, sex and time since the Alzheimer’s disease diagnosis. All proton pump inhibitors available in Finland were investigated.

The analyses were adjusted for other medication increasing the risk of fall, osteoporosis, socioeconomic status, long-term hospital care, history of psychiatric diseases, and chronic diseases increasing the risk of fall or fracture.

A pill combining low doses of three blood pressure-lowering medications significantly increased the number of patients reaching blood pressure targets compared with usual care, researchers reported at the American College of Cardiology’s 67th Annual Scientific Session. There was also no significant increase in adverse effects with the “Triple Pill.”

“Most people—70 percent—reached blood pressure targets with the Triple Pill. The benefits were seen straight away and maintained until six months, whereas with usual care control rates were 55 percent at six months and even lower earlier in the trial,” said Ruth Webster, MBBS, of The George Institute for Global Health at the University of New South Wales in Sydney, Australia, and lead author of the study. “Based on our findings, we conclude that this new method of using blood pressure-lowering drugs was more effective and just as safe as current approaches.”

Despite the availability of effective blood pressure-lowering drugs, high blood pressure remains a major problem around the world, Webster said. Effectively treating high blood pressure can help to prevent heart attacks, strokes and kidney problems. Globally, however, many people with high blood pressure receive no treatment, and only about a third of those who are treated achieve recommended reductions in blood pressure. Achieving desired reductions in blood pressure often requires treatment with more than one medication, which increases the complexity of treatment, and patients often have difficulty adhering to regimens that involve taking multiple pills every day.

This study was the first large trial designed to test the theory that starting treatment with low doses of three drugs could achieve better blood pressure control compared with usual care and that combining these drugs in a single pill would make it easier both for doctors to prescribe treatment and for patients to adhere to it, Webster said.

The TRIUMPH trial, which was conducted in Sri Lanka, enrolled 700 patients whose average age was 56 years, 58 percent of whom were women. Trial participants had an average blood pressure of 154/90 mm Hg. Over half (59 percent) were receiving no treatment for high blood pressure before they enrolled in the trial. In addition to high blood pressure, 32 percent of participants had diabetes or chronic kidney disease.

Patients were randomly assigned to receive either the combination pill or usual care. The combination pill, or Triple Pill, consisted of the blood pressure medications telmisartan (20 mg), amlodipine (2.5 mg) and chlorthalidone (12.5 mg). These medications use different mechanisms to reduce blood pressure by relaxing the blood vessels, so the heart does not need to pump as hard to send blood throughout the body. Usual care meant that patients received their doctor’s choice of blood pressure­-lowering medication.

The trial’s primary endpoint was the proportion of patients who achieved a blood pressure target of 140/90 mm Hg or less (130/80 mm Hg or less in those with diabetes or chronic kidney disease) at six months.

Compared with patients receiving usual care, a significantly higher proportion of patients receiving the Triple Pill achieved their target blood pressure at six months. The average reduction in blood pressure was 8.7 mm Hg for participants receiving the Triple Pill and 4.5 mm Hg for those receiving usual care. At six months, 83 percent of participants in the Triple Pill group were still receiving the combination pill and one-third of those in the usual-care group were receiving at least two blood pressure-lowering drugs.

The maximum difference between the two groups of patients was observed at six weeks after starting treatment, when 68 percent of those receiving the Triple Pill had achieved a blood pressure within their target range, compared with 44 percent of those receiving usual care. This represented a 53 percent reduction in the risk for high blood pressure for patients receiving the Triple Pill, Webster said.

Rates of participants having to change treatment due to side effects were not significantly different in the two groups (6.6 percent for the Triple Pill, 6.8 percent for usual care). This should allay concerns that use of the three-drug combination pill could lead to an unacceptable increase in adverse medication side effects, Webster said.

Each of the drugs used in the Triple Pill has been shown to be highly effective in reducing blood pressure and preventing deaths and illness due to heart disease and strokes, she said. Each drug represents a different class of blood pressure medication and previous studies have shown that combining such drugs results in synergistic effects.

“The most urgent need for innovative strategies to control blood pressure is in low- and middle-income countries,” Webster said. “The Triple Pill approach is an opportunity to ‘leap frog’ over traditional approaches to care and adopt an innovative approach that has been shown to be effective.”

The study’s findings are also important for high-income countries, she said.

“A control rate of 70 percent would be a considerable improvement even in high-income settings. Most hypertension guidelines in these countries do not recommend combination blood pressure-lowering therapy for initial treatment in all people,” she said. “Our findings should prompt reconsideration of recommendations around the use of combination therapy.”

An inevitable consequence of a necessarily unblinded study (where both participants and their doctors know whether participants are assigned to the Triple Pill or usual care) is that doctors might manage patients differently depending on the assigned treatment. However, it is important to note this trial was designed to evaluate a new strategy of care in a real-world setting, Webster said.

To minimize the risk of bias in measuring the main outcomes, the number of patient visits was identical in both groups and all outcomes were standardized and objectively documented, she said.

The researchers are now conducting a follow-up qualitative study to find out what participants and their doctors thought about using the Triple Pill. And they are conducting a cost effectiveness evaluation to determine whether the Triple Pill is a cost-effective solution for blood pressure control.

Recommended targets for blood pressure control vary by country. In the U.S., guidance released in 2017 by the ACC and the American Heart Association recommends initiating treatment if blood pressure exceeds 130/80 mm Hg. European guidelines recommend that treatment should aim to achieve a blood pressure level of 140/90 mm Hg or less.

The combined rate of death from any cause, heart attack or stroke within 18 months was not significantly different in patients with acute coronary syndrome (ACS) who were randomly assigned to receive dual antiplatelet therapy (DAPT) for either six months or at least 12 months after receiving a drug-eluting stent. Patients who were given DAPT for only six months, however, had more than double the risk of a heart attack compared with those treated for at least 12 months, according to research presented at the American College of Cardiology’s 67th Annual Scientific Session.

“Based on our findings, we can’t say that short-term DAPT is safe in patients with ACS who have received drug-eluting stents,” said Hyeon Cheol Gwon, MD, a professor in the Division of Cardiology at Sungkyunkwan University, director of the cardiac center at Samsung Medical Center in Seoul, South Korea, and principal investigator of the study. “We conclude that current guidelines that recommend prolonged DAPT in patients with ACS who are not at excessive risk for bleeding should continue to be followed.”

ACS occurs when blood flow to the heart is suddenly blocked. It may take the form of a heart attack or unstable angina, chest pain that may signal an imminent heart attack. Patients who have had one episode of ACS are at elevated risk for another. ACS is often treated by inserting a small metal tube, or stent, into a blocked artery to keep the artery open, a procedure known as an angioplasty. A drug-eluting stent is a stent that has been coated with a drug to prevent scar tissue from forming inside the artery.

Current guidelines published by the American College of Cardiology and the American Heart Association recommend that ACS patients not at excessive risk for bleeding should be treated with DAPT— aspirin plus clopidogrel or a similar drug such as ticagrelor—for at least 12 months after the implantation of a drug-eluting stent.

However, there is limited evidence that 12 months or more is the optimal duration for DAPT, Gwon said. Two recently reported studies suggested that six months of DAPT might offer similar benefits in terms of reducing patients’ risk for death, heart attack or stroke, bleeding or other adverse events. These studies, however, had too few participants to provide definitive answers, he said.

“This is the largest trial to address the optimal duration of DAPT in patients with ACS,” Gwon said.

The SMART-DATE trial enrolled a total of 2,712 Korean patients with ACS who were undergoing angioplasty. Their median age was 63 years, and 75 percent were male. Patients were randomly assigned to receive either DAPT for at least 12 months (DAPT-12) or DAPT for six months followed by aspirin alone for at least another six months (DAPT-6). The primary endpoint was the combined rate of death from any cause, heart attack or stroke within 18 months after stent insertion.

At 18 months, 63 patients (4.7 percent) in the DAPT-6 group and 56 patients (4.2 percent) in the DAPT-12 group had experienced at least one of the primary endpoint events. Thus, over the entire 18-month follow-up period, DAPT-6 was significantly not worse (or non-inferior) than DAPT-12, Gwon said. Rates of death from any cause were not significantly different in the two groups (2.6 percent in the DAPT-6 group vs 2.9 percent in the DAPT-12 group).

However, the risk of heart attack was 2.4-fold higher in the DAPT-6 group, with heart attacks occurring in 1.8 percent of DAPT-6 patients vs. 0.8 percent of DAPT-12 patients. Moreover, during the period between six and 18 months after stent insertion when patients in the DAPT-6 group were being treated with aspirin only, there was a 5.1-fold risk of having a heart attack in DAPT-6 patients compared with DAPT-12 patients. During this period, patients in the DAPT-6 group also had a 69 percent higher risk of dying from any cause or having a heart attack or stroke.

Limitations of the study, Gwon said, include the absence of blinding— that is, both patients and doctors knew whether a patient was in the DAPT-6 or the DAPT-12 group—and the absence of a group that was randomly assigned to receive a placebo. However, study statisticians and those whose role was to assess outcomes worked independently from those overseeing the trial, he said.

Patients in the trial will be followed for an additional 18 months, for a total of three years of follow-up, Gwon said.

After six months of follow up, women newly diagnosed with breast cancer who were given the beta blocker carvedilol to prevent heart issues while undergoing chemotherapy showed no difference in declines in heart function compared with those taking a placebo. Patients who took carvedilol, however, were significantly less likely to have an elevated marker in the blood that signals injury to the heart, according to a study being presented at the American College of Cardiology’s 67th Annual Scientific Session.\

The study enrolled 200 patients diagnosed with breast cancer who had normal left ventricular ejection fraction and who, as part of their cancer treatment, were scheduled to receive anthracycline (ANT). Patients were randomly assigned to receive either carvedilol (median daily dose of 18.4 mg/day) or placebo when starting ANT chemotherapy (240 mg/m2) until completing it. ANT is a type of chemotherapy that at certain cumulative doses has been shown to cause heart damage by weakening the heart muscle. Carvedilol works by slowing the heart rate, opening blood vessels and improving blood flow, which also lowers blood pressure.

“This is the largest randomized clinical trial of a beta blocker to prevent the toxic effects of contemporary doses of anthracycline [ANT] on the heart,” said Mônica Samuel Avila, MD, assistant doctor in the Heart Failure and Heart Transplant Department in Heart Institute, Clinical Hospital of Medical School of São Paulo, and the study’s lead author. “This is only short-term follow up, but we found that carvedilol seems to prevent myocardial injury, but it did not have an impact on left ventricular ejection fraction.”

Avila also said the study findings further reinforce the need for cardiologists and oncologists to work together to define the best treatment strategies for individual cancer patients that minimize other negative effects, especially to the heart.

Neither the patients nor those administering the treatment knew which patients received carvedilol versus the placebo. Researchers assessed cardiotoxicity by measuring heart function with periodic echocardiograms and blood tests to check for a protein called high-sensitivity troponin T, which is released into the bloodstream when injury to the heart occurs. These measures were tracked at baseline and after each cycle of ANT chemotherapy (three, six, nine and 12 weeks) and after the end of all chemotherapy (around 24 weeks). Patients in the carvedilol and placebo groups were an average of 51 and 53 years of age, respectively. All had finished chemotherapy treatment.

For the study’s primary endpoint, prevention of greater than a 10 percent reduction in left ventricular ejection fraction at six months, researchers found no significant difference between the carvedilol and placebo groups, 14.5 vs. 13.5 percent, respectively. Ejection fraction is a measure of how much blood is pumped out of the heart with each contraction; anything over 55 percent is considered normal. Overall, declines in ejection fraction were minimal in both groups and were not statistically significant (from baseline to 24 weeks the average drop in ejection fraction was 65.2 to 63.9 percent in the placebo group and 64.8 to 63.9 percent in the carvedilol group).

Secondary outcomes included carvedilol’s effects on two biomarkers, troponin I and B-type natriuretic peptide (BNP), and diastolic dysfunction. Of the 65 (33.8 percent) patients with higher plasma levels of troponin I that are known to be suggestive of heart damage, many more were in the placebo group—41.6 percent vs. 26 percent. There was no difference in levels of BNP, a hormone produced by the heart that goes up when heart failure develops or gets worse. While not significant, patients in the placebo group tended to have enlarged hearts, compared to patients in the carvedilol group. Avila said this could indicate that carvedilol may help prevent remodeling or changes in the structure of the heart.

According to Avila, the reason why patients taking carvedilol had lower troponin levels, but no differences in changes in ejection fraction, is difficult to explain. She noted that the six-month follow-up may not have been sufficient to see changes in heart function. In addition, any heart damage may not have been severe enough to lead to heart failure. There was only one case of overt heart failure with reduced ejection fraction, which was in the placebo group.

“Previous studies have shown that higher troponin levels can predict cardiovascular events and so we could imagine that carvedilol may be able to prevent these events, but we did not see this finding in our study,” she said, adding that she and her team will continue to follow these patients and report data at one and two years.

In the meantime, researchers did find the prevalence of cardiotoxicity in this study to be lower than in previously reported data from other studies—a finding that could be attributed to lower doses of anthracyclines and lower overall cardiovascular risk in the study population. It could be that the beneficial effect of carvedilol might be more pronounced among higher risk patients, Avila said. In recent years, lower doses of anthracyclines are used to help reduce the risk of heart damage from treatment.

Source: American College of CardiologyFull bibliographic information:Carvedilol for Prevention of Chemotherapy Related CardiotoxicityJournal of the American College of Cardiology

Getting a large dose of a statin did not have an impact on major adverse cardiac events among a broad population of patients slated to undergo percutaneous coronary intervention (PCI) in a trial being presented at the American College of Cardiology’s 67th Annual Scientific Session. However, statins did significantly reduce the rates of such events among the subset of trial participants who actually underwent PCI.

PCI is one of several treatments for people with acute coronary syndrome, an umbrella term that encompasses heart attacks and unstable angina. In this trial, patients were randomized to receive either a placebo or a “loading dose” of a statin, consisting of two double-doses administered the day before and the day after a scheduled PCI, followed by a daily low-dose of a statin for 30 days.

The trial is the largest study to date aimed at testing the hypothesis that statins could help reduce cardiovascular events around the time of PCI. More than 4,100 patients were enrolled in the trial at 58 centers in Brazil. All patients had acute coronary syndrome for which doctors planned to perform PCI within seven days. However, about one-third of the study participants ultimately did not receive PCI because doctors opted to perform other treatments, such as coronary artery bypass grafting.

Participants in this study were reflective of the broader population of people with acute coronary syndrome, and the study protocols were reflective of common hospital practices, said Otavio Berwanger, MD, PhD, cardiologist and clinical epidemiologist at the Brazilian Clinical Research Institute, Sao Paulo, Brazil, and the study’s lead author. He suggested that the results would likely be applicable in many countries and health care environments. About 70 percent of the patients had never taken statins and about 30 percent had taken them previously or were on low-dose statins when they enrolled in the study. Patients who were already taking a maximum tolerated dose of statins were excluded.

Statins are a widely-used class of drugs that lower LDL, or “bad” cholesterol, thereby helping to prevent serious cardiovascular events in people at high risk for heart disease. In addition to their long-term preventive benefits, basic research suggests statins also may affect processes involved in inflammation and the formation of blood clots.

In this study, half of the participants were randomly assigned to receive two double (80 milligram) doses of atorvastatin—one shortly before the procedure and one within a day afterward. The other half received two doses of a placebo. Neither patients nor their doctors knew who had received the placebo. All patients then took 40 milligrams of atorvastatin daily for 30 days, which is standard practice after acute coronary syndrome.

Among all patients, the primary endpoint occurred in 6.2 percent of those taking the statin and 7.1 percent of those taking the placebo, a difference that was not statistically significant. Among patients who received PCI, the primary endpoint occurred in 6 percent of those taking the statin and 8.2 percent of those taking the placebo, a reduction that was statistically significant.

“Although the trial is negative for our primary endpoint in the full study population, the findings of our prespecified analysis are very consistent with smaller trials and observational studies that suggest a reduction in events in the PCI population,” Berwanger said. “Viewed in the context of the literature, our study helps to confirm what has been shown before and suggests that it can be beneficial to consider giving a loading dose of a statin to patients who undergo PCI.”

Overall, patients who underwent PCI and received a loading dose of statins were 28 percent less likely to experience a major adverse cardiac event and 32 percent less likely to have a heart attack compared with those taking the placebo.

“This study adds another piece to the puzzle,” Berwanger said. “I think it also opens the stage for testing other lipid-lowering agents that may have effects beyond lowering lipids.”

Researchers will continue to track outcomes for 12 months. In addition, the team is planning another trial focused on assessing potential benefits of statins and other drugs in patients undergoing PCI.

Source: American College of CardiologyFull bibliographic information:Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial

Treatment with dabigatran significantly reduced the risk of death, heart attack, stroke and other heart or blood-vessel complications among patients who were at elevated risk for these events because of heart damage that occurred after major noncardiac surgery, according to research being presented at the American College of Cardiology’s 67th Annual Scientific Session.

In the first randomized controlled trial to evaluate a treatment for myocardial injury after noncardiac surgery (MINS), researchers found that patients treated with dabigatran twice daily were 28 percent less likely to die, have a heart attack or stroke, develop blood clots or need an amputation due to cardiovascular disease, compared with patients who received a placebo.

“We have shown for the first time that dabigatran reduces the risk of major cardiovascular complications and offers an option for improving outcomes in a large at-risk population who have MINS,” said P.J. Devereaux, MD, PhD, director of cardiology at McMaster University in Hamilton, Canada, and lead author of the study.

Approximately 8 million people every year develop MINS after undergoing surgery such as a hip or knee replacement, bowel resection or abdominal aortic aneurysm repair.

This study builds on research that Devereaux and his colleagues presented at the American College of Cardiology’s 66th Annual Scientific Session in 2017 showing that MINS may account for about 1 in 4 deaths during the first 30 days after surgery. That research also showed a blood test for a protein called high-sensitivity troponin T, which is released into the bloodstream when injury to the heart occurs, can identify patients with MINS whose lives could potentially be saved with timely treatment.

Most cases of MINS currently go undetected, Devereaux said, because at present it is not standard practice in most centers to monitor blood levels of troponin in patients who had major noncardiac surgery. Devereaux said he is hopeful this will change now that this study has shown treatment with dabigatran can improve outcomes for patients with MINS.

“Our findings reaffirm that patients who develop MINS are at high risk for bad outcomes,” he said. “We owe it to our patients to identify this risk and do what we can to reduce it.”

The study enrolled 1,754 patients in 19 countries, 51 percent of whom were men, with an average age of 70 years. The primary efficacy outcome was the combined rate of death from a cardiovascular cause, heart attack, stroke due to inadequate blood supply, blood clots or amputation due to cardiovascular disease. The primary safety outcome was the combined rate of life-threatening, major and critical organ bleeding. During the study, patients, health care providers and research staff were blinded to which group received dabigatran and which received a placebo.

After an average follow-up of 16 months, 11.1 percent of patients treated with dabigatran experienced one or more of the primary efficacy outcome events, compared with 15.2 percent of patients who received a placebo. This translates to a 28 percent reduction in risk for patients receiving dabigatran.

When researchers analyzed occurrence rates for the events comprising the primary efficacy outcome, they found trends of benefit for each component. For example, patients treated with dabigatran were 20 percent less likely to die of a cardiovascular cause, 20 percent less likely to have a heart attack, 30 percent less likely to have an amputation and 53 percent less likely to have a venous blood clot than patients who received a placebo. The result for nonhemorrhagic stroke also demonstrated a benefit with an 80 percent reduction in risk, a difference that was statistically significant compared with patients who were randomized to placebo.

There were no statistically significant differences between the two groups in life-threatening, major or critical organ bleeding. Compared with the placebo group, however, more patients in the dabigatran group experienced bleeding in the lower gastrointestinal tract and minor bleeding.

An increased risk of bleeding is an expected complication of treatment with a blood-thinning medication.

“It’s encouraging that we did not see an increase in major or life-threatening bleeding in patients on dabigatran,” Devereaux said.

Researchers noted that while nearly all patients (98.9 percent) completed follow-up, 45.3 percent of those on dabigatran had discontinued the study drug. The most common reason for drug discontinuation was patient request; however, 14 percent of these patients had a major complication (e.g., heart attack, stroke, bleeding). According to Devereaux, analyses that counted patients up to seven days after they discontinued the study drug showed even larger treatment effects, with 46 percent reductions in major cardiovascular complications with dabigatran and no excess of life-threatening, major or critical organ bleeding.

Devereaux said that future research is needed to evaluate other treatment options for this high-risk group of patients.

Listening to upbeat music may help prolong activity and participation; results may have broader implications for exercise in general

If you exercise while listening to music, you may have noticed it can help boost your energy and make your workout seem quicker. Similarly, a study being presented at the American College of Cardiology’s 67th Annual Scientific Session suggests listening to music during a standard cardiac stress test can help extend the time someone is able to perform the test, yielding important information about an individual’s heart health and capacity for exercise.

Music can have a powerful impact on our mood, signaling the brain to release feel-good and energy-boosting chemicals. While earlier studies have looked at how music might influence specific markers of heart health, this study is the first to evaluate its impact on exercise tolerance during cardiac stress testing—widely used to measure the effects of exercise on the heart. On average, people who listened to music during the test were able to exercise for almost one minute longer than those who didn’t have tunes playing in their ears.

“At least on a small scale, this study provides some evidence that music may help serve as an extra tool to help motivate someone to exercise more, which is critical to heart health,” said Waseem Shami, MD, a cardiology fellow at Texas Tech University Health Sciences in El Paso, Texas, and the study’s lead author. “I think it’s something we intuitively knew, but we found [to be true]. I suspect if it had been a larger study, we’d see a bigger difference.”

Cardiac stress tests help doctors evaluate someone’s fitness level or readiness to start an exercise program, measure heart rate and blood pressure responses to exercise, assess symptoms of chest pain or heart rhythm changes during exercise, and help diagnose blockages in the heart’s arteries. They are often done on a treadmill or stationary bike, while a person has electrodes placed on their chest to record the heart’s activity.

In this single-center, randomized study, patients scheduled for a routine electrocardiogram (ECG) treadmill stress test were informed about the study and asked if they would participate. A total of 127 patients (53 years of age on average) were randomly assigned to either listen to up-tempo music (mostly Latin-inspired music) or have no music playing during their stress tests. To “blind” the staff and clinicians, all participants wore headphones during their test. Individuals had similar medical histories, including diabetes and hypertension. The majority of participants were Hispanic, reflecting their patient population. There were more females than males in both groups (61.2 and 66.7 percent in the music and control groups, respectively).

Shami explained that stress tests can be challenging—even painful—for some people because the treadmill speed and incline is increased every three minutes. In the standard Bruce protocol, the starting point (i.e., stage 1) is 1.7 mph at a 10 percent grade (5 METs). Stage 2 is 2.5 mph at a 12 percent grade (7 METs). Stage 3 is 3.4 mph at a 14 percent grade (9 METs). This protocol includes three-minute periods to allow achievement of a steady state before workload is increased.

“After six minutes, you feel like you are running up a mountain, so even being able to go 50 seconds longer means a lot,” he said. Although the maximum duration for a stress test is 20 minutes, Shami said most healthy people usually last for seven to eight minutes.

Exercise time was significantly longer in the music group compared with the control group, 505.8 versus 455.2 seconds, respectively—an absolute difference of about 50.6 seconds. In addition, there was a (non-significant) trend toward longer metabolic equivalent of task (METs) when compared with the non-music group. A MET is a ratio of the rate of energy expended during an activity to the rate of energy used at rest. Generally, the higher the number, the more energy used and the harder someone worked.

There were no differences in how often patients were able to reach their maximal target heart rate goal between the two groups, which was one of the reasons Shami and team designed the pilot study.

Although the study involved people undergoing cardiac stress testing, Shami said he believes the findings could apply to a wider population and help motivate people to follow recommendations for regular exercise for heart health.

“Our findings reinforce the idea that upbeat music has a synergistic effect in terms of making you want to exercise longer and stick with a daily exercise routine,” he said. “When doctors are recommending exercise, they might suggest listening to music too.”

Being inactive or not exercising ranks alongside high blood pressure, high cholesterol, smoking and obesity as one of the five major risk factors for cardiovascular disease. Getting regular exercise may be one of the best defenses against heart disease or having another cardiac event. Experts recommend adults get at least 30 minutes of moderate (aerobic) activity most days; this includes taking a brisk walk, swimming, playing tennis, riding a bicycle, dancing, water aerobics, gardening and even busy housework.

Shami said a larger study with greater diversity is needed to be able to determine whether offering music during stress testing can help people achieve their target heart rate and if it should be recommended as a tool to help people.

Source: American College of Cardiology

Full bibliographic information:Shami will present the study, “Does Music Impact Exercise Capacity During Cardiac Stress Test? A Single Blinded Pilot Randomized Controlled Study,” American College of Cardiology's 67th Annual Scientific Session.